Search

Megacities are major sources of anthropogenic fossil fuel CO2 (FFCO2) emissions. The spatial extents of these large urban systems cover areas of 10 000 km2 or more with complex topography and changing landscapes. We present a high-resolution land-atmosphere modelling system for urban CO2 emissions over the Los Angeles (LA) megacity area. The Weather Research and Forecasting (WRF)-Chem model was coupled to a very high-resolution FFCO2 emission product, Hestia-LA, to simulate atmospheric CO2 concentrations across the LA megacity at spatial resolutions as fine as ∼ 1 km. We evaluated multiple WRF configurations, selecting one that minimized errors in wind speed, wind direction, and boundary layer height as evaluated by its performance against meteorological data collected during the CalNex-LA campaign (May-June 2010). Our results show no significant difference between moderate-resolution (4 km) and high-resolution (1.3 km) simulations when evaluated against surface meteorological data, but the high-resolution configurations better resolved planetary boundary layer heights and vertical gradients in the horizontal mean winds. We coupled our WRF configuration with the Vulcan 2.2 (10 km resolution) and Hestia-LA (1.3 km resolution) fossil fuel CO2 emission products to evaluate the impact of the spatial resolution of the CO2 emission products and the meteorological transport model on the representation of spatiotemporal variability in simulated atmospheric CO2 concentrations. We find that high spatial resolution in the fossil fuel CO2 emissions is more important than in the atmospheric model to capture CO2 concentration variability across the LA megacity. Finally, we present a novel approach that employs simultaneous correlations of the simulated atmospheric CO2 fields to qualitatively evaluate the greenhouse gas measurement network over the LA megacity. Spatial correlations in the atmospheric CO2 fields reflect the coverage of individual measurement sites when a statistically significant number of sites observe emissions from a specific source or location. We conclude that elevated atmospheric CO2 concentrations over the LA megacity are composed of multiple fine-scale plumes rather than a single homogenous urban dome. Furthermore, we conclude that FFCO2 emissions monitoring in the LA megacity requires FFCO2 emissions modelling with ∼ 1 km resolution because coarser-resolution emissions modelling tends to overestimate the observational constraints on the emissions estimates.

AIM: This paper reports a study to determine whether a nurse-initiated telephone follow-up programme could increase patients' self-efficacy in managing dyspnoea and decrease health care service use. BACKGROUND: Chronic obstructive pulmonary disease is a worldwide health problem and has been labelled a burdensome disease. Because of the fear of activity-induced dyspnoea, patients with chronic obstructive pulmonary disease lack the confidence to perform daily activities. Studies of cardiac and diabetic patients have shown that telephone follow-up care is an effective approach to increasing self-efficacy. However, little such research has been done with patients with chronic obstructive pulmonary disease. METHODS: This was a randomized controlled study. A total of 60 participants (30 telephone follow-up, 30 control) with chronic obstructive pulmonary disease were recruited from an acute care hospital in Hong Kong. The Chinese Self-Efficacy Scale was used to assess self-efficacy. Measures of health care use were numbers of visits to an accident and emergency department, hospitalizations, and unscheduled visits by physicians. FINDINGS: The self-efficacy scores (U = 272.5, P = 0.009) of patients who were followed up by telephone improved significantly compared with those of patients in the control group. Multiple regression analyses showed that telephone follow-up (Beta = 0.33, CI: 0.19-0.48, P = 0.001), the pulmonary rehabilitation programme (Beta = 0.44, CI: 0.16-0.72, P = 0.003), smoking (Beta = 0.34, CI: 0.09-0.57, P = 0.009), and health care use (Beta = -0.27, CI: -0.47-(-0.07), P = 0.008) were significant factors in predicting patient self-efficacy. CONCLUSIONS: Nurse-initiated telephone follow-up care was effective in increasing self-efficacy in managing dyspnoea. The study needs to be replicated in other setting to strengthen its external validity. [ABSTRACT FROM AUTHOR]

Visibility can be interpreted as the largest distance of an object that can be recognized or detected under a bright environment that can be used as an environmental indicator for weather conditions and air pollution. The accuracy of the classical approach of visibility calculation, in which meteorological laws and image feature extraction from digital images are used, depends on the quality and noise disturbances of the image. Therefore, artificial intelligence (AI) and digital image approaches have been proposed for visibility estimation in the past. Image features for the whole digital image are generated by pre-trained convolutional neural networks, and the Artificial Neural Network (ANN) is designed for correlation between image features and visibilities. Instead of using the information of the whole digital images, past research has been proposed to identify effective subregions from which image features are generated. A generalized regression neural network (GRNN) was designed to correlate the image features with the visibilities. Past research results showed that this method is more accurate than the classical approach of using handcrafted features. However, the selection of effective subregions of digital images is not fully automated and is based on manual selection by expert judgments. In this paper, we proposed an automatic effective subregion selection method using landmark object extraction techniques. Image features are generated from these LMO subregions, and the ANN is designed to approximate the mapping between LMO regions' feature values and visibility values. The experimental results show that this approach can minimize the reductant information for ANN training and improve the accuracy of visibility estimation as compared to the single image approach.

For emergency medicine physicians, being named in a malpractice suit is not an if, it is a when. By the age of 55 years, 68% of emergency physicians have been sued. In the following article, we review the most common factors shared by closed claims in adult and pediatric patients from emergency departments and acute care settings. Our hope is that by identifying shared characteristics, we may improve patient care and reduce litigation risk., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Circuit dysfunction in autism may involve a failure of homeostatic plasticity. To test this, we studied parvalbumin (PV) interneurons which exhibit rapid homeostatic plasticity of intrinsic excitability following whisker deprivation in mouse somatosensory cortex. Brief deprivation reduces PV excitability by increasing Kv1 current to increase PV spike threshold. We found that PV homeostatic plasticity is disrupted in Tsc2 +/- and Fmr1 -/- models of autism. In wildtype mice, deprivation elevates the transcription factor ER81 which drives Kcna1 transcription, increasing Kv1.1 protein in the axon initial segment and soma. These molecular signatures of homeostasis were absent in Tsc2 +/- and Fmr1 -/- . Whisker enrichment increased PV excitability, but not in Tsc2 +/- , indicating that homeostasis is lost bidirectionally. Deprivation reduced feedforward L4-L2/3 inhibition in wildtype but not Tsc2 +/- mice. Thus, two autism models show a convergent loss of PV circuit homeostasis at physiological and molecular levels, potentially contributing to sensory processing impairments.

High spatial or temporal variability in community composition makes it challenging for natural resource managers to predict ecosystem trajectories at scales relevant to management. This is commonly the case in nearshore marine environments, where the frequency and intensity of disturbance events vary at the sub-kilometer to meter scale, creating a patchwork of successional stages within a single ecosystem. The successional stage of a community impacts its stability, recovery potential, and trajectory over time in predictable ways. Here we demonstrate the value of successional theory for interpreting fine-scale community heterogeneity using Hawaiian coral reefs as a case study. We tracked benthic community dynamics on 36 forereefs over a 6-year period (2017-2023) that captures impacts from high surf events, a marine heatwave, and unprecedented shifts in human behavior due to the COVID-19 pandemic. We document high spatial variation in benthic community composition that was only partially explained by island and environmental regime. Through hierarchical clustering, we identify three distinct community types that appear to represent different successional stages of reef development. Reefs belonging to the same community type exhibited similar rates of change in coral cover and structural complexity over time, more so than reefs located on the same island. Importantly, communities that were indicative of early succession (low coral cover reefs dominated by stress-tolerant corals) were most likely to experience an increase in coral cover over time, while later-stage successional communities were more likely to experience coral decline. Our findings highlight the influence of life history and successional stage on community trajectories. Accounting for these factors, not simply overall coral cover, is essential for designing effective management interventions. Site-specific management that accounts for a community's unique composition and history of disturbance is needed to effectively conserve these important ecosystems., (Global Change Biology© 2025 The Author(s). Global Change Biology published by John Wiley & Sons Ltd.)

Background/purpose: Various pulp-covering materials offer advantages in regenerative root canal treatment, but each has limitations, highlighting the need for more effective antibacterial strategies for pulp repair and regeneration. Mesoporous bioactive glasses (MBG) show significant biological activity, making them valuable in tissue/dental repair. Silver-incorporated MBG exhibits promising antibacterial effects against various bacteria; copper ions are crucial in regulating angiogenesis signals. Co-loading copper and silver in bioactive glasses has been explored to address clinical challenges. This study modified the preparation of silver-copper bimetallic mesoporous bioactive glass, analyzing their textural properties and antibacterial activity against Enterococcus faecalis ., Materials and Methods: The silver-copper co-loaded bioactive glass (designated as AgCu/80S) was synthesized using a sol-gel technique with modifications. Textural analyses were carried out via X-ray diffraction, UV-Vis spectroscopy, Brunauer-Emmett-Teller analysis, and transmission electron microscope. The ion-releasing activity determined using inductively coupled plasma-mass spectrometry, and the antibacterial activity against E. faecalis was assessed through disk diffusion and kinetic bacterial growth curve., Results: The modification led to weaker crystallization of calcium silicate, altering ion-releasing and antibacterial activities. Ag3Cu2/80S exhibited the highest released silver ion concentration at 112.6 ppm, with an inhibition zone of 9.09 ± 0.09 mm in disk diffusion assays. However, the inhibition zone of Ag2Cu3/80S was 9.92 ± 0.04 mm, implying that the antibacterial activity may not only be influenced by silver ions., Conclusion: The AgCu/80S showed a potential antibacterial activity against E. faecalis , whereas further research on AgCu/80S glasses is necessary to optimize ion release conditions, assess bioactivities, and explore potential dental applications., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.Vé.)

Embryonic stem cells possess the remarkable ability to self-organize into blastocyst-like structures upon induction. These stem cell-based embryo models serve as invaluable platforms for studying embryogenesis and therapeutic developments. Nevertheless, the specific intrinsic regulators that govern this potential for blastoid formation remain unknown. Here we demonstrate an intrinsic program that plays a crucial role in both blastoids and blastocysts across multiple species. We first establish metrics for grading the resemblance of blastoids to mouse blastocysts, and identify the differential activation of gene regulons involved in lineage specification among various blastoid grades. Notably, abrogation of nuclear receptor subfamily 1, group H, member 2 (Nr1h2) drastically reduces blastoid formation. Nr1h2 activation alone is sufficient to rewire conventional ESC into a distinct pluripotency state, enabling them to form blastoids with enhanced implantation capacity in the uterus and contribute to both embryonic and extraembryonic lineages in vivo. Through integrative multi-omics analyses, we uncover the broad regulatory role of Nr1h2 in the transcriptome, chromatin accessibility and epigenome, targeting genes associated with embryonic lineage and the transposable element SINE-B1. The Nr1h2-centred intrinsic program governs and drives the development of both blastoids and early embryos., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Antibodies to select Epstein-Barr virus proteins can diagnose early-stage nasopharyngeal carcinoma (NPC). We have previously shown that IgA against Epstein-Barr virus nuclear antigen 1 (EBNA1) can predict incident NPC in high- and intermediate-risk cohorts 4 years before diagnosis. Here, we tested EBNA1 variants, with mutants, to define the sequence requirements for an NPC risk assay., Experimental Design: Mammalian-expressed constructs were developed to represent EBNA1 variants 487V and 487A, which can differ by ≥15 amino acids in the N- and C-termini. Denatured lysates were evaluated by a refined IgA and IgG immunoblot assay in a case-control study using prediagnostic NPC sera from two independent cohorts in Singapore and Shanghai, the People's Republic of China., Results: At 95% sensitivity, 487V yielded a 94.9% specificity compared with 86.1% for 487A. EBNA1 deleted for the conserved glycine-alanine repeats (GAr) reduced false positives by 22.8%. NPC sera reacted more strongly to the C-terminus than healthy controls, but the C-terminal construct (a.a. 390-641) showed lower specificity (84.8%) than the EBNA1 GAr-deleted construct (92.4%) at 95% sensitivity., Conclusions: Although EBNA1 IgA was present in healthy sera, most epitopes localized to the immunodominant GAr. We conclude that a refined EBNA1 antigen deleted for the GAr, but with residues consistently detected in Southeast Asian NPC tumors, is optimized for risk prediction with an extended sojourn time of 7.5 years. Furthermore, distinct EBNA1 serologic profiles enhanced the utility of the EBNA1 IgA assay for risk stratification. This illustrates the importance of serologically relevant EBNA1 sequences for NPC risk prediction and early detection., (©2024 American Association for Cancer Research.)

Background Calcific uremic arteriolopathy (CUA) is a rare but debilitating disease affecting patients with kidney disease. Reported risk factors of CUA in the literature include female sex, obesity, diabetes mellitus, and vitamin K antagonists' (VKAs) usage. CUA prevalence in Malaysia is unknown and has not been reported before. Methods A multicenter observational study was conducted in 13 centers all over Malaysia to study the clinical characteristics, treatment, and outcomes of CUA. The data of patients confirmed with CUA between January 1, 2016, and December 31, 2021, was collected from medical records by each center's nephrologists. Results Out of 33 confirmed CUA cases, 69.7% were females, and 66.7% were Malay with a mean age of 47.33 ± 13.80 years old. The mean BMI was 25.66 ± 9.77 kg/m 2 , and 18.2% were classified as obese (BMI > 30). Two-thirds of the patients were on hemodialysis (HD), and the mean dialysis vintage was 6.2 ± 4.11 years. A majority (87.9%) have hypertension, 33.3% are diabetic, and 27.3% have coronary artery disease. Only 15.2% of the patients were on warfarin at the time of diagnosis. A total of 78.8% of patients were taking calcium-based phosphate binders during diagnosis. Investigation results showed calcium, 2.44 ± 0.29 mmol/L; phosphate, 2.18 ± 0.67 mmol/L; CaXPO4 = 5.41 ± 1.90; and parathyroid hormone, 181.14 ± 153.23 pmol/L. About half (54.5%) had skin biopsy confirmation done. Distribution of lesions was 57.6% peripheral and 30.3% central. For treatment of CUA, there were 57.6% usage of non-calcium-based phosphate binders, 48.5% cinacalcet, 30.3% sodium thiosulphate, and 33.3% had parathyroidectomy. Half (54.5%) of our CUA patients died within three months from diagnosis. The mean time from diagnosis to mortality was 4.12 ± 5.59 months. A majority (45.5%) died from septicemia caused by infections. Interestingly, there were a few rare presentations of CUA such as pulmonary calciphylaxis, heart and lung calcifications, liver and spleen calcifications, and genital lesions. One patient had resistant CUA and was given a trial of lipid apheresis for 10 sessions. Conclusion This is the first and largest multicenter study looking into the characteristics, treatment, and outcome of CUA in Malaysia. Majority of patients in Malaysia undergo HD as kidney replacement therapy; hence, our results correlate with this. The incidence of CUA was estimated to be 6.6 per 10,000 dialysis patients in this study and the mortality rate is very high. This is consistent with worldwide data which reported mortality as high as 60%., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. University of Malaya Medical Centre Medical Research Ethics Committee issued approval 2021922-10603. This study protocol was reviewed and approved by the University of Malaya Medical Centre Medical Research Ethics Committee, with approval number 2021922-10603. Requirement for informed consent was waived due to the retrospective nature of the study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Lee et al.)

Key Clinical Message: Lumbar facet fracture-dislocation is rare, often due to hyperflexion with rotational force. Abnormal scoliosis on radiography is a key sign, prompting further imaging. Facetectomy and laminectomy ensure safe reduction, while instrumented fusion is an effective surgical treatment., Abstract: Traumatic lumbar facet dislocation is an uncommon condition, particularly when unilateral lumbar facet dislocation is accompanied by a contralateral facet fracture. The patient had a locked facet joint at the left L4-L5, a fracture of the right superior articular process of L5 and a comminuted fracture at the peritrochanteric region of the right femur following a fall. Emergent operation was conducted, starting with open reduction and fixation for the right proximal femur, followed by posterior open reduction and posterolateral fusion with instrumentation, without interbody fusion, for the lumbar spine injury. The patient exhibited positive outcomes throughout the follow-up. This article highlights the trauma mechanism of lumbar facet dislocation, emphasizing hyperflexion with rotational force. Abnormal local scoliosis is a distinctive imaging sign of facet joint dislocation. Facetectomy and laminectomy are recommended for safe reduction and instrumented fusion is considered a safe and effective surgical treatment for facet joint dislocation injuries., Competing Interests: None of the authors had any conflict of interest in relation to this report., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Wearable haptics serve as an enhanced media to connect humans and VR/robots. The inevitable sweating issue in all wearables creates a bottleneck for wearable haptics, as the sweat/moisture accumulated in the skin/device interface can substantially affect feedback accuracy, comfortability, and create hygienic problems. Nowadays, wearable haptics typically gain performance at the cost of sacrificing the breathability, comfort, and biocompatibility. Here, we developed a fully integrated breathable haptic textile (FIBHT) to solve these trade-off issues, where the FIBHT exhibits high-level integration of 128 pixels over the palm, great stretchability of 400%, and superior permeability of over 657 g/m 2 /day (moisture) and 40 mm/s (air). It is a stand-alone haptic system totally composed of stretchable, breathable, and bioadhesive materials, which empowers it with precise, sweating/movement-insensitive and dynamic feedback, and makes FIBHT powerful for virtual touching in broad scenarios.

Background: Metabolic surgery is recognized for its effectiveness in weight loss and improving outcomes for individuals with type 2 diabetes mellitus (T2DM). However, its impact on renal function, especially in multi-ethnic Asian populations, remains underexplored. This study investigates mid- and long-term renal outcomes following metabolic surgery in Asian patients with T2DM., Methods: This retrospective cohort study utilized data from the Asian Diabetes Surgery Study (ADSS), involving T2DM patients aged 20-79 who underwent metabolic surgery from 2008 to 2015. The primary outcome was the change in estimated glomerular filtration rate (eGFR) at 1, 3, and 5 years post-surgery, with adjustments for confounders. Secondary outcomes included changes in chronic kidney disease (CKD) stages and the relationship between weight loss and eGFR changes. Data were analyzed using univariate and multivariable regression analyses, along with the McNemar test., Results: The study included 1513 patients with a mean age of 42.7 years. The results revealed that a significant improvement in eGFR was observed at 1-year post-surgery (112.4 ± 32.0 ml/min/1.73 m², P  < .001), with a shift toward less severe CKD stages. However, this improvement was not sustained at 3 and 5 years. No significant correlation was found between weight loss and eGFR changes at 1-year follow-up., Conclusion: Metabolic surgery significantly improves renal function at 1 year postoperatively in Asian individuals with T2DM, highlighting its potential benefits beyond glycemic control and weight loss. The long-term effects on renal function require further investigation., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Objective: Mass Casualty Incidents (MCIs) involving high-speed passenger ferries (HSPFs) may result in the dual-wave phenomenon, in which the emergency department (ED) is overwhelmed by an initial wave of minor injuries, followed by a second wave of more seriously injured victims. This study aimed to characterize the time pattern of ED presentation of victims in such accidents in Hong Kong., Methods: All HSPF MCIs from 2005 to 2015 were reviewed retrospectively, with the time interval from accident to ED registration determined for each victim. Multivariable linear regression was used to identify independent factors associated with the time of ED presentation after the accidents., Results: Eight MCIs involving 492 victims were identified. Victims with an Injury Severity Score (ISS) ≥ 9 had a significantly shorter median time interval compared to those with minor injuries. An ISS ≥ 9 and evacuation by emergency service vessels were associated with a shorter delay in ED arrival, whereas ship sinking, accident at nighttime, and a longer linear distance between the accident and receiving ED were associated with a longer delay., Conclusion: The dual-wave phenomenon was not present in HSPF MCIs. Early communication is the key to ensure early resource mobilisation and a well-timed response.

Given a maze (e.g., in a book of puzzles), you might solve it by drawing out paths with your pencil. But even without a pencil, you might naturally find yourself mentally tracing along various paths. This "mental path tracing" may intuitively seem to depend on your (overt, conscious, voluntary) goal of wanting to get out of the maze, but might it also occur spontaneously-as a result of simply seeing the maze, via a kind of dynamic visual routine? Here, observers simply had to compare the visual properties of two probes presented in a maze. The maze itself was entirely task irrelevant, but we predicted that simply seeing the maze's visual structure would "afford" incidental mental path tracing (à la Gibson). Across four experiments, observers were slower to compare probes that were further from each other along the paths, even when controlling for lower level properties (such as the probes' brute linear separation, ignoring the maze "walls"). These results also generalized beyond mazes to other unfamiliar displays with task-irrelevant circular obstacles. This novel combination of two prominent themes from our field-affordances and visual routines-suggests that at least some visual routines may not require voluntary goals; instead, they may operate in an automatic (incidental, stimulus-driven) fashion, as a part of visual processing itself. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objective: To evaluate the factors that improve professional and personal well-being amongst women in neonatology (WiN)., Study Design: A 30-question survey of multiple choice, rank order, and open-ended questions focused on professional and personal factors that affect the well-being of WiN members. Quantitative and qualitative methods were used to determine leading factors and themes., Results: Of 326 respondents, 64% felt "well" professionally over half of the time. Professional well-being was most affected by scheduling flexibility, helping patients, administrative and staffing support, feelings of being valued, and clinical workload/acuity. Time for family and self-care, having domestic help, and scheduling flexibility were factors that most positively impacted personal well-being., Conclusion: In this national survey, WiN members identified the factors that can improve their well-being. Strategic planning and targeted interventions are urgently needed to enhance work-life integration and job satisfaction, leading to improved neonatal workforce retention and improved quality of patient care., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Autologous bone dust can be filled in bone defects to promote effective bone healing but typically it is lost when using suction during surgery. The aim of this study was to develop a novel bone collector that can be used to collect bone chips/dust of varying sizes without changing current surgical procedures., Research Design and Methods: This collector was designed to connect to a surgical continuous suction system and comprised a plate filter with a 3 mm hole and featured a taper filter with a mesh size of 0.27 mm for the separation and collection of both coarse and fine bone chips/dust. The bone collector was manufactured using nylon 3D printing and plastic injection with biocompatible materials., Results: The bone collector functional test revealed high bone chip collection efficiency (93%) with automatic size separation function. Low (3.42%) filtration errors showed that most of the water can be drained smoothly from the bone collector. In clinical usability testing, bone collectors can provide functions demonstrated in in vivo spinal fusion and femoral fracture surgeries with different bone grafting size requirements., Conclusions: The novel bone collector has been validated as a viable and effective surgical device, offering surgeons an additional option to enhance patient outcomes.

Tuberculosis-affected lungs with chronic inflammation harbor abundant immunosuppressive immune cells but the nature of such inflammation is unclear. Dysfunction in T cell exhaustion, while implicated in chronic inflammatory diseases, remains unexplored in tuberculosis. Given that immunotherapy targeting exhaustion checkpoints exacerbates tuberculosis, we speculate that T cell exhaustion is dysfunctional in tuberculosis. Using integrated single-cell RNA sequencing and T cell receptor profiling we reported defects in exhaustion responses within inflamed tuberculosis-affected lungs. Tuberculosis lungs demonstrated significantly reduced levels of exhausted CD8+ T cells and exhibited diminished expression of exhaustion-related transcripts among clonally expanded CD4+ and CD8+ T cells. Additionally, clonal expansion of CD4+ and CD8+ T cells bearing T cell receptors specific for CMV was observed. Expanded CD8+ T cells expressed the cytolytic marker GZMK. Hence, inflamed tuberculosis-affected lungs displayed dysfunction in T cell exhaustion. Our findings likely hold implications for understanding the reactivation of tuberculosis observed in patients undergoing immunotherapy targeting the exhaustion checkpoint., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Genetic variants in Epstein-Barr virus (EBV) have been strongly associated with nasopharyngeal carcinoma (NPC) in South China. However, different results regarding the most significant viral variants, with polymorphisms in EBER2 and BALF2 loci, have been reported in separate studies. In this study, we newly sequenced 100 EBV genomes derived from 61 NPC cases and 39 population controls. Comprehensive genomic analyses of EBV sequences from both NPC patients and healthy carriers in South China were conducted, totaling 279 cases and 227 controls. Meta-analysis of genome-wide association study revealed a 4-bp deletion downstream of EBER2 (coordinates, 7188-7191; EBER-del) as the most significant variant associated with NPC. Furthermore, multiple viral variants were found to be genetically linked to EBER-del forming a risk haplotype, suggesting that multiple viral variants might be associated with NPC pathogenesis. Population structure and phylogenetic analyses further characterized a high risk EBV lineage for NPC revealing a panel of 38 single nucleotide polymorphisms (SNPs), including those in the EBER2 and BALF2 loci. With linkage disequilibrium clumping and feature selection algorithm, the 38 SNPs could be narrowed down to 9 SNPs which can be used to accurately detect the high risk EBV lineage. In summary, our study provides novel insight into the role of EBV genetic variation in NPC pathogenesis by defining a risk haplotype of EBV for downstream functional studies and identifying a single high risk EBV lineage characterized by 9 SNPs for potential application in population screening of NPC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)